TGF-β Signaling in Myeloid Cells Is Required for Tumor Metastasis

被引：140

作者：

Pang, Yanli ^{[1
]}

Gara, Sudheer Kumar ^{[1
]}

Achyut, Bhagelu R. ^{[1
]}

Li, Zhaoyang ^{[1
]}

Yan, Hannah H. ^{[1
]}

Day, Chi-Ping ^{[1
]}

Weiss, Jonathan M. ^{[2
]}

Trinchieri, Giorgio ^{[2
]}

Morris, John C. ^{[3
]}

Yang, Li ^{[1
]}

机构：

[1] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA

[2] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA

[3] Univ Cincinnati, Dept Med, Div Hematol Oncol, Cincinnati, OH 45221 USA

来源：

CANCER DISCOVERY | 2013年 / 3卷 / 08期

关键词：

GROWTH-FACTOR; SUPPRESSOR-CELLS; IMMUNE CELLS; DENDRITIC CELLS; BREAST-CANCER; MOUSE MODEL; T-CELLS; MACROPHAGES; EXPRESSION; MECHANISM;

D O I：

10.1158/2159-8290.CD-12-0527

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

TGF-beta is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-beta functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2(MyeK0)) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2(MyeK0) bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-beta 1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-gamma production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2(MyeK0) mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-beta receptor II expression. Our studies show that myeloid-specific TGF-beta signaling is an essential component of the metastasis-promoting puzzle of TGF-beta. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.

引用

页码：936 / 951

页数：16

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